Covering the whole development process for the global biotechnology industry

Bioprocessing begins upstream, most often with culturing of animal or microbial cells in a range of vessel types (such as bags or stirred tanks) using different controlled feeding, aerating, and process strategies.

Beginning with harvest of material from a bioreactor, downstream processing removes or reduces contaminants to acceptable levels through several steps that typically include centrifugation, filtration, and/or chromatographic technologies.

Drug products combine active pharmaceutical ingredients with excipients in a final formulation for delivery to patients in liquid or lyophilized (freeze-dried) packaged forms — with the latter requiring reconstitution in the clinical setting.

Many technologies are used to characterize biological products, manufacturing processes, and raw materials. The number of options and applications is growing every day — with quality by design (QbD) giving impetus to this expansion.

Even as it matures, the biopharmaceutical industry is still a highly entrepreneurial one. Partnerships of many kinds — from outsourcing to licensing agreements to consultancies — help companies navigate this increasingly global business environment.

New technologies bring new regulatory challenges. The biopharmaceutical industry must be cautious in its implementation of new scientific ideas and technology platforms — no matter how promising those might be. Regulators will look skeptically on any claim that isn’t backed up by good data, and with no solid history of successful use to build on, a company must have all the answers itself. How do compliance professionals anticipate what kinds of questions reviewers will ask when the time comes — and how can those in development laboratories and manufacturing suites best be prepared to respond to them? With all that in mind, this eBook addresses a number of new approaches to the regulation-defined areas of chemistry, manufacturing, and controls (CMC) for protein biologics.

Many new product modalities are challenging the old ways of thinking and doing things, and new bioprocess and analytical technologies can offer solutions to the problems they introduce. Meanwhile, those new technologies also suggest new methodologies for established and familiar product types. Changing legacy processes may not be feasible in most cases (because of associated regulatory hurdles), but the overall paradigm will shift over time as advanced platforms are applied to new projects going forward.

Ultimately all work performed under current good manufacturing practice (CGMP) must follow proper standard operating procedures (SOPs), including required documentation for eventual inclusion in regulatory filings such as biological license applications (BLAs). In this eBook, I have arranged sections on chemistry (product characterization, formulation, and cell-line development), manufacturing (platforms, single-use technologies, and continuous processing), and controls (modeling, process control, and data management) not to exactly reflect the regulations, but rather to follow a logical framework for discussion. From a regulatory standpoint, “CMC” sections are those parts of a filing that do not address preclinical and clinical product testing results.